Characterizing the cellular and molecular variabilities of peripheral immune cells in healthy recipients of BBIBP-CorV inactivated SARS-CoV-2 vaccine by single-cell RNA sequencing

Abstract

Over 3 billion doses of inactivated vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been administered globally. However, our understanding of the immune cell functional transcription and T cell receptor (TCR)/B cell receptor (BCR) repertoire dynamics following inactivated SARS-CoV-2 vaccination remains poorly understood. Here, we performed single-cell RNA and TCR/BCR sequencing on peripheral blood mononuclear cells at four time points after immunization with the inactivated SARS-CoV-2 vaccine BBIBP-CorV. Our analysis revealed an enrichment of monocytes, central memory CD4 + T cells, type 2 helper T cells and memory B cells following vaccination. Single-cell TCR-seq and RNA-seq comminating analysis identified a clonal expansion of CD4 + T cells (but not CD8 + T cells) following a booster vaccination that corresponded to a decrease in the TCR diversity of central memory CD4 + T cells and type 2 helper T cells. Importantly, these TCR repertoire changes and CD4 + T cell differentiation were correlated with the biased VJ gene usage of BCR and the antibody-producing function of B cells post-vaccination. Finally, we compared the functional transcription and repertoire dynamics in immune cells elicited by vaccination and SARS-CoV-2 infection to explore the immune responses under different stimuli. Our data provide novel molecular and cellular evidence for the CD4 + T cell-dependent antibody response induced by inactivated vaccine BBIBP-CorV. This information is urgently needed to develop new prevention and control strategies for SARS-CoV-2 infection. (ClinicalTrials.gov Identifier: NCT04871932).

The characteristics of BCR‐CDR3 repertoire in COVID‐19 patients and SARS‐CoV‐2 vaccinated volunteers

“…Moreover, there is a strong correlation between the length of H‐CDR3 and IgG1, IgA2, and IgM subtypes following vaccination. Tong et al 62 found the frequency of 18 AA H‐CDR3 and 13 AA L‐CDR3 elevated after the administration of the second dose of BBIBP‐CorV for 14 days. These suggested relatively large differences in the molecular mechanisms of individual B‐cell responses after SARS‐CoV‐2 infection and vaccine administration.…”

“…The CSR after SARS‐CoV‐2 vaccination is not completely consistent with that of COVID‐19 patients. Fraley et al 51 found no significant change in isotype proportion after Pfizer‐mRNA vaccination, with no difference between the positive and negative groups; Tong et al 62 discovered that the abundance of IGHA and IGHG increased after the BBIBP‐CorV vaccine administration. Kotagiri et al 42 reported a rise in the proportions of IgD and IgM subtypes, along with a decrease in IgG2, IgA1, and IgE levels following 25 days of BNT162b2 vaccination, while there was a notable increase in IgG1, IgG3, and IgA1 levels following 25 days of TIV vaccination.…”

“…Brouwer et al 60 discovered SARS-CoV-2 S protein-specific B cells enriched H-CDR3 with more than 20 AA; Gao et al 46 reported the length of H-CDR3 ranged from 4 to 47 AA in COVID-19 patients infected by Wuhan strain, and the frequency of H-CDR3 with longer than 17 AA is higher compared to the healthy controls; Zhang et al 47 observed a significant increase in the mean length of H-CDR3 in COVID-19 patients after the second week, followed by a decrease at 3 months post-recovery; Galson et al 40 The CSR after SARS-CoV-2 vaccination is not completely consistent with that of COVID-19 patients. Fraley et al 51 found no significant change in isotype proportion after Pfizer-mRNA vaccination, with no difference between the positive and negative groups; Tong et al 62 discovered that the abundance of IGHA and IGHG increased after the BBIBP-CorV vaccine administration. Kotagiri et al 42 reported a rise in the proportions of IgD and IgM subtypes, along with a decrease in IgG2, IgA1, and IgE levels following 25 days of BNT162b2 vaccination, while there was a notable increase in IgG1, IgG3, and IgA1 levels following 25 days of TIV vaccination.…”

Single-cell multiomics analysis reveals SARS-CoV-2 inactivated vaccine-induced trained immunity modulated by epigenetic remodeling

“…Vaccine is one of the most cost-effective strategies to cope with the pandemic and reduce mortality with inactivated whole-virus and mRNA vaccines being the most widely deployed vaccine types 2,3 . Despite intensive clinical studies concerning the immunogenicity of vaccines and immunological studies dissecting the immune signaling of vaccineelicited immune response [4][5][6][7][8][9] , we know little about the epigenetic regulatory mechanism of vaccine-elicited immune responses, particularly time-and cell-type-resolved gene regulations that mediate immune responses to SARS-CoV-2 vaccine 10,11 .…”

Breakthrough infection evokes the nasopharyngeal innate immune responses established by SARS-CoV-2–inactivated vaccine

“…Despite the effectiveness of anti-viral drugs in preventing severe disease and reducing mortality, promoting and popularizing vaccines are the most vital ways to impede virus spread (1,2). Similar to recovered patients with COVID-19, vaccinated subjects (including those vaccinated with mRNA and inactivated SARS-CoV-2 vaccines) displayed an efficient induction of virus-specific T-cell responses and neutralizing antibodies among a wide range of tissues, such as peripheral blood, lymph nodes, and upper respiratory tract mucous (3)(4)(5)(6)(7)(8)(9)(10). This might rationally explain the restrained virus replication, shedding, tissue localization (11), and even the clinically reported decline of severe incidence and mortality after vaccination (4,(12)(13)(14).…”